The epidemic of AIDS/HIV infection and its consequences have profoundly and irrevocably affected all aspects of biomedical science and health care practice, including dentistry. The dynamic and changing nature of the epidemic is reflected in new populations infected or at risk, longer life spans of those with HIV infection due to changing retroviral therapy and prophylaxis or to treatment of HIV complications, and behavioral changes among those at risk, patients and health-care providers. This continuing evolution of AIDS and of the response to the pandemic is remarkably reflected in the patterns among patients, those at risk, providers and investigators in San Francisco, a city among those most affected by this disease. AIDS and HIV infection cause a wide range of serious oral lesions, of significance in the biology and natural history of HIV infection, which we have investigated for several years. This renewal application prpopses a series of integrated and multidisciplinary, yet focused and specific, studies which build on the achievements of the Oral AIDS Center at the University of California, San Francisco. The proposal is submitted by a group of clinical, epidemiological and laboratory investigators whose coordinated research on oral manifestations of AIDS/HIV infection has been innovative and productive. It proposes new approaches in response to the changing challenges posed by the epidemic. We seek to understand the role of oral lesions in the context of the changing demographics of the epidemic; their significance in relation to new assays for HIV viral load and to changes in the natural history of HIV infection; and the effects of continually changing therapy directed at HIV or its complications. We seek to advance understanding of Epstein-Barr virus (EBV) infection in hairy leukoplakia and Candida albicans. by pursuing strategies that will allow examination at the cellular and molecular levels of the dynamic interactions between host and pathogen that result in disease. We thus propose a group of three integratd multidisciplinary studies based on the unusual, perhaps unique, opportunity presented by our group to explore the interface of oral disease, epidemiology and molecular pathology. These three coordinated components will be supported by the administrative core and the clinical/laboratory core.